Beta-lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae.

TitleBeta-lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae.
Publication TypeJournal Article
Year of Publication2001
AuthorsConrath, K. E., M. Lauwereys, M. Galleni, A. Matagne, J. M. Frère, J. Kinne, L. Wyns, and S. Muyldermans
JournalAntimicrob Agents Chemother
Volume45
Issue10
Pagination2807-12
Date Published2001 Oct
ISSN0066-4804
KeywordsAmino Acid Sequence, Ampicillin, Animals, Antibody Specificity, Bacterial Proteins, beta-Lactamases, Camels, Escherichia coli, Immunoglobulin Fragments, Male, Molecular Sequence Data, Penicillin Resistance, Penicillins, Protein Structure, Tertiary, Sequence Homology, Amino Acid
Abstract

Small, soluble single-domain fragments derived from the unique variable region of dromedary heavy-chain antibodies (VHHs) against enzymes are known to be potent inhibitors. The immunization of dromedaries with the TEM-1 and BcII beta-lactamases has lead to the isolation of such single-domain antibody fragments specifically recognizing and inhibiting those beta-lactamases. Two VHHs were isolated that inhibit TEM-1 and one BcII inhibiting VHH was identified. All inhibitory VHHs were tight-binding inhibitors. The 50% inhibitory concentrations were determined for all inhibitors and they were all in the same range as the enzyme concentration used in the assay. Addition of the VHHs to the TEM-1 beta-lactamase, expressed on the surface of bacteria, leads to a higher ampicillin sensitivity of the bacteria. This innovative strategy could generate multiple potent inhibitors for all types of beta-lactamases.

DOI10.1128/AAC.45.10.2807-2812.2001
Alternate JournalAntimicrob. Agents Chemother.
PubMed ID11557473
PubMed Central IDPMC90735